A Randomized, Double-blind, Placebo-controlled Study of the JAK Inhibitor INCB018424 Tablets Administered Orally to Subjects With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 309
- 主要终点
- Number of Participants Achieving ≥ 35% Reduction in Spleen Volume From Baseline to Week 24
研究概览
简要总结
This was a randomized, double-blind study comparing the efficacy and safety of ruxolitinib (INCB018424) tablets to matching placebo tablets in patients diagnosed with Myelofibrosis (either Primary Myelofibrosis (PMF) or Post-Polycythemia Vera Myelofibrosis (PPV-MF) or Post-Essential Thrombocythemia Myelofibrosis (PET-MF).
详细描述
Patients with spleen growth of greater than 25% based on an increase in spleen volume from Baseline were eligible for early unblinding, and for patients on placebo, cross over to ruxolitinib prior to the primary study endpoint being reached. If this spleen growth occurred before Week 24, it must have been accompanied by specific worsening of symptoms, based on worsening early satiety accompanied by weight loss or worsening pain requiring daily narcotic use. After Week 24, asymptomatic spleen growth alone was sufficient for early unblinding and potential cross over. Patients found to have been randomized to ruxolitinib after early unblinding prior to Week 24 were discontinued.
When half of the patients remaining in the study completed the Week 36 visit and all patients enrolled completed Week 24 or discontinued, the database was frozen and the primary analysis was conducted. Once this was complete, all patients were unblinded and patients who had been randomized to placebo were given the opportunity to cross over to ruxolitinib treatment, provided hematology laboratory parameters were adequate; Patients receiving benefit could continue treatment until the later of marketing approval or when the last randomized patient remaining in the study had completed Week 144 (36 months).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must be diagnosed with primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) or post-essential thrombocythemia-myelofibrosis (PET-MF) according to the 2008 World Health Organization criteria
- •Subjects with myelofibrosis requiring therapy must be classified as high risk OR intermediate risk level 2 according to the prognostic factors defined by the International Working Group
- •Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 or 3
- •Subjects who have not previously received treatment with a Janus kinase (JAK) inhibitor
排除标准
- •Subjects with a life expectancy of less than 6 months
- •Subjects with inadequate bone marrow reserve as demonstrated by specific clinical laboratory counts
- •Subjects with inadequate liver or renal function
- •Subjects with clinically significant bacterial, fungal, parasitic or viral infection which require therapy
- •Subjects with an active malignancy over the previous 5 years except specific skin cancers.
- •Subjects with severe cardiac conditions
- •Subjects who have had splenic irradiation within 12 months
研究组 & 干预措施
Ruxolitinib
Participants received ruxolitinib orally twice a day. The starting dose was determined based on Baseline platelet count. Patients with Baseline platelet count > 200,000/μL began a dose regimen of 20 mg twice daily. Patients with Baseline platelet count of 100,000/μL to 200,000/μL (inclusive) began a dose regimen of 15 mg twice daily. The dose was adjusted by the Investigator based on efficacy and safety to a maximum of 25 mg twice daily. Patients receiving benefit could continue treatment until the later of marketing approval or when the last randomized patient remaining in the study had completed Week 144 (36 months).
干预措施: Ruxolitinib (Drug)
Placebo
Placebo tablets matching ruxolitinib were administered orally twice a day at a starting dose based on Baseline platelet count. Doses were titrated using the same guidelines as for active drug. Patients meeting certain protocol requirements detailed below were given the opportunity to cross over to ruxolitinib treatment.
干预措施: Ruxolitinib (Drug)
Placebo
Placebo tablets matching ruxolitinib were administered orally twice a day at a starting dose based on Baseline platelet count. Doses were titrated using the same guidelines as for active drug. Patients meeting certain protocol requirements detailed below were given the opportunity to cross over to ruxolitinib treatment.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants Achieving ≥ 35% Reduction in Spleen Volume From Baseline to Week 24
时间窗: Baseline and Week 24
Spleen volume was assessed by magnetic resonance imaging (MRI) or by computed tomography (CT) scans if MRI was not suitable, and analyzed by a blinded central laboratory reader. Patients who withdrew, crossed over to ruxolitinib prior to the visit, or had a missing value at the visit were considered non-responders.
次要结局
- Duration of Maintenance of a ≥ 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib(Baseline Visit and every 12 weeks until the data cut-off date (up to 14 months).)
- Number of Participants With a ≥ 50% Reduction in Total Symptom Score From Baseline to Week 24(Baseline and Week 24. Baseline total score was the average of the daily total scores for the last 7 days prior to randomization. The Week 24 total score was the average of daily total scores from the 28 days prior to the Week 24 visit.)
- Maintenance of a ≥ 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib(Baseline Visit and every 12 weeks until the data cut-off date (up to 14 months).)
- Overall Survival - Extended Data(From randomization to 4 months after the data cut-off date (up to 18 months).)
- Overall Survival Time - Extended Data(From randomization to 4 months after the data cut-off date (up to 18 months).)
- Change From Baseline to Week 24 in Total Symptom Score(Baseline and Week 24. Baseline total score was the average of the daily total scores for the last 7 days prior to randomization. The Week 24 total score was the average of daily total scores from the 28 days prior to the Week 24 visit.)
- Overall Survival(From randomization to the data cut-off date (up to 14 months).)
- Overall Survival Time(From randomization to the data cut-off date (up to 14 months).)
- Overall Survival at Week 144(Week 144)
- Overall Survival Time at Week 144(Week 144)